• BMB Reports
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• v.48 no.6
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• pp.319-323
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• 2015

Mesenchymal stem cells (MSCs) are multipotent stem cells capable of differentiating into adipocytes, osteoblasts, or chondrocytes. A mutually inhibitory relationship exists between osteogenic and adipogenic lineage commitment and differentiation. Such cell fate decision is regulated by several signaling pathways, including Wnt and bone morphogenetic protein (BMP). Accumulating evidence indicates that microRNAs (miRNAs) act as switches for MSCs to differentiate into either osteogenic or adipogenic lineage. Different miRNAs have been reported to regulate a master transcription factor for osteogenesis, such as Runx2, as well as molecules in the Wnt or BMP signaling pathway, and control the balance between osteoblast and adipocyte differentiation. Here, we discuss recent advancement of the cell fate decision of MSCs by miRNAs and their targets. [BMB Reports 2015; 48(6): 319-323]

• IMMUNE NETWORK
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• v.23 no.1
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• pp.4.1-4.15
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• 2023

Th cells, which orchestrate immune responses to various pathogens, differentiate from naive CD4 T cells into several subsets that stimulate and regulate immune responses against various types of pathogens, as well as a variety of immune-related diseases. Decades of research have revealed that the fate decision processes are controlled by cytokines, cytokine receptor signaling, and master transcription factors that drive the differentiation programs. Since the Th1 and Th2 paradigm was proposed, many subsets have been added to the list. In this review, I will summarize these events, including the fate decision processes, subset functions, transcriptional regulation, metabolic regulation, and plasticity and heterogeneity. I will also introduce current topics of interest.

• Molecules and Cells
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• v.42 no.12
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• pp.836-839
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• 2019

A tumor is an abnormal mass of tissue that arises when cells divide more than they should or do not die when they should. The cellular decision regarding whether to undergo division or death is made at the restriction (R)-point. Consistent with this, an increasingly large body of evidence indicates that deregulation of the R-point decision-making machinery accompanies the formation of most tumors. Although the R-point decision is literally a matter of life and death for the cell, and thus critical for the health of the organism, it remains unclear how a cell chooses its own fate. Recent work demonstrated that the R-point constitutes a novel oncogene surveillance mechanism operated by R-point-associated complexes of which RUNX3 and BRD2 are the core factors (Rpa-RX3 complexes). Here, we show that not only RUNX3 and BRD2, but also other members of the RUNX and BRD families (RUNX1, RUNX2, BRD3, and BRD4), are involved in R-point regulation.

• BMB Reports
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• v.48 no.4
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• pp.223-228
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• 2015

The Drosophila lymph gland is the hematopoietic organ in which stem-like progenitors proliferate and give rise to myeloid-type blood cells. Mechanisms involved in Drosophila hematopoiesis are well established and known to be conserved in the vertebrate system. Recent studies in Drosophila lymph gland have provided novel insights into how external and internal stresses integrate into blood progenitor maintenance mechanisms and the control of blood cell fate decision. In this review, I will introduce a developmental overview of the Drosophila hematopoietic system, and recent understandings of how the system uses developmental signals not only for hematopoiesis but also as sensors for stress and environmental changes to elicit necessary blood responses. [BMB Reports 2015; 48(4): 223-228]

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2003.05a
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• pp.149-149
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• 2003

To understand environmental paths of the transport and accumulation of endocrine disrupting chemicals (EDCs), a single cell multimedia fate model has been constructed and evaluated. The EDCs of concern were PAHs, Organochlorine Pesticides (OCPs), PCBs, Alkyl phenols, and phthalates. An evaluation model was designed for the multimedia distribution, including air, water, soil, sediment and vegetation. This model was verified using reported values and via monitoring data. Based on collected data, the distribution trends of EDCs with respect to environmental media were analyzed. Those results have applied to the model for the prediction of the spatial and temporal distribution of EDCs in Seoul. Especially, phenol compound, phthalates, PAHs, PCBs and organochlorine pesticides were estimated and the model was verified. This model was successfully conducted to environmental media, such as air (vapor and suspended particles), soils (forest soil, bare soil, and cement-concrete covered soil), water (dissolved and suspended solids), sediment, trees (deciduous and coniferous). The discrepancies between the model prediction and the measured data are approximately within or near a factor of 10 for the PAHs of three rings through that of six rings, implying that multimedia distribution of the PAHs could be predicted with a factor of 10. Concerning about the air equilibrium may be assumed, a fugacity at steady state is similar in all environmental media. Considering the uncertainties of this model, the use of equilibrium models may be sufficient for assessing chemical fates. In this study, a suggestion was made that modeling and estimation of chemicals in environmental multimedia be rigorously evaluated using the measured flux data. In addition, these data should be obtained, for example, from the precise and standardized inventory of the target chemicals. The model (EDC Seoul) will be refined in an on-going research effort and will be used to support decision-making concerning the management of EDCs.

• International Journal of Stem Cells
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• v.16 no.3
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• pp.293-303
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• 2023

Background and Objectives: The physiological oxygen tension in fetal brains (~3%, physioxia) is beneficial for the maintenance of neural stem cells (NSCs). Sensitivity to oxygen varies between NSCs from different fetal brain regions, with midbrain NSCs showing selective susceptibility. Data on Hif-1𝛼/Notch regulatory interactions as well as our observations that Hif-1𝛼 and oxygen affect midbrain NSCs survival and proliferation prompted our investigations on involvement of Notch signalling in physioxia-dependent midbrain NSCs performance. Methods and Results: Here we found that physioxia (3% O₂) compared to normoxia (21% O₂) increased proliferation, maintained stemness by suppression of spontaneous differentiation and supported cell cycle progression. Microarray and qRT-PCR analyses identified significant changes of Notch related genes in midbrain NSCs after long-term (13 days), but not after short-term physioxia (48 hours). Consistently, inhibition of Notch signalling with DAPT increased, but its stimulation with Dll4 decreased spontaneous differentiation into neurons solely under normoxic but not under physioxic conditions. Conclusions: Notch signalling does not influence the fate decision of midbrain NSCs cultured in vitro in physioxia, where other factors like Hif-1𝛼 might be involved. Our findings on how physioxia effects in midbrain NSCs are transduced by alternative signalling might, at least in part, explain their selective susceptibility to oxygen.

• Molecules and Cells
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• v.21 no.2
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• pp.218-223
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• 2006

The effect of poly(ADP-ribosyl)ation on the stability of p53 in SK-HEP1 cells treated with UV light was examined. Intracellular levels of p53 increased in cells treated with a low dose of UV light ($20J/m^2$), whereas they increased but then declined after a higher dose of UV ($100J/m^2$). Intracellular levels of p53 in the UV treated SK-HEP1 cells were dependent on the UV dose. Use of proteasome inhibitors revealed that p53 is degraded by proteasomal proteolysis after high doses of UV light. We present evidence that, at low doses, poly(ADP-ribose)polymerase (PARP) poly(ADP-ribosyl) ates p53 and protects it from proteasomal degradation before caspase-3 is activated, whereas at high doses the cells undergo UV induced apoptosis and PARP is cleaved by caspase-3 before it can protect p53 from degradation. Destabilization of p53 by cleavage of PARP may be important in cell fate decision favoring apoptosis.

• Journal of Microbiology and Biotechnology
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• v.22 no.4
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• pp.571-573
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• 2012

Glyceraldehyde-3-phosphate (G-3-P), the substrate of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), is a key intermediate in several metabolic pathways. Recently, we reported that G-3-P directly inhibits caspase-3 activity in a reversible noncompetitive mode, suggesting the intracellular G-3-P level as a cell fate decision factor. It has been known that apoptotic stimuli induce the generation of NO, and NO S-nitrosylates GAPDH at the catalytic cysteine residue, which confers GAPDH the ability to bind to Siah-1, an E3 ubiquitin ligase. The GAPDH-Siah-1 complex is translocated into the nucleus and subsequently triggers the apoptotic process. Here, we clearly showed that intracellular G-3-P protects GAPDH from S-nitrosylation at above a certain level, and consequently maintains the cell survival. In case G-3-P drops below a certain level as a result of exposure to specific stimuli, G-3-P cannot inhibit S-nitrosylation of GAPDH anymore, and consequently GAPDH translocates with Siah-1 into the nucleus. Based on these results, we suggest that G-3-P functions as a molecule switch between cell survival and apoptosis by regulating S-nitrosylation of GAPDH.

• Development and Reproduction
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• v.9 no.2
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• pp.105-114
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• 2005

Embryonic stem(ES) cells have tremendous potential as a cell source for cell-based therapies. Realization of that potential will depend on our ability to understand and manipulate the factors that influence cell fate decision and to develop methods for getting enough cell numbers for clinical applications. Hematopoiesis has been widely studied, and hematopoietic differentiation from ES cells is a good model to study lineage commitment. In this study, we investigated stemness and compared the efficiency of hematopoietic differentiation using two different mouse embryonic stem cell lines TC-1 and B6-1. Although the two cell lines showed known stem cell properties with minor differences, the embryoid body formation efficiency in methylcellulose was much higher in TC-1 than B6-1. When measured potentials of hematopoietic differentiation using functional(colony-forming cell) and phenotypic(specific marker expression) assays, we found that TC-1 can differentiate into hematopoietic cells in methylcellulose culture but B6-1 cannot. These results imply that we can improve the efficiency of hematopoietic cell differentiation by selection of proper cell lines and this may be also applied in the differentiation of human embryonic stem cells.

• BMB Reports
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• v.45 no.3
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• pp.153-158
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• 2012

Geft is a guanine nucleotide exchange factor, which can specifically activate Rho family of small GTPase by catalyzing the exchange of bound GDP for GTP. Geft is highly expressed in the excitable tissue as heart and skeletal muscle and plays important roles in many cellular processes, such as cell proliferation, migration, and cell fate decision. However, the in vivo role of Geft remains unknown. Here, we generated a Geft conditional knockout mouse by flanking exons 5-17 of Geft with loxP sites. Cre-mediated deletion of the Geft gene in heart using Mef2c-Cre transgenic mice resulted in a dramatic decrease of Geft expression. Geft knockout mice develop normally and exhibit no discernable phenotype, suggesting Geft is dispensable for the development of the second heart field in mouse. The Geft conditional knockout mouse will be a valuable genetic tool for uncovering the in vivo roles of Geft during development and in adult homeostasis.